Long-term follow-up of patients with frontalis sling operation in the treatment of essential blepharospasm unresponsive to botulinum toxin therapy

Objective Botulinum toxin is the treatment of choice in patients with essential blepharospasm, but about 4% of patients show no sufficient effect. Many of these patients try to open their eyes by innervating their frontalis muscle. This led to the idea of performing frontalis suspension, normally used for certain types of ptosis. We set out to evaluate the long-term results, complication rates and patient acceptance of this intervention.Methods Frontalis sling operation was carried out on 252 eyes of 132 blepharospasm patients between 1992 and 2004. In all patients botulinum toxin treatment was administered before surgery with no or only brief and incomplete effect even with increasing toxin doses. In 120 patients surgery was performed under local anaesthesia, while 12 patients were operated upon under general anaesthesia (mostly bilateral). Silk sutures were employed in the first 14 eyes, and in all others we used Gore-Tex suture material.Results The duration of follow-up was 3–154 months; 60 patients were followed up for at least 5 years. Seventy-three per cent of patients reported an improvement after surgery. Long-term subjective improvement showed a median of 50% on a scale ranging from 0%=no improvement to 100%=no complaints. No serious corneal complications occurred, although slight overcorrection is desirable in the first days after surgery for a satisfactory long-term result. Seven per cent of operations had to be revised due to suture granulomas or extruded suture material. The effect of surgery generally remained stable over the years, with most patients needing additional treatment with botulinum toxin. In cases of decreasing effect (5% of eyes), the sutures were tightened under local anaesthesia.Conclusion Frontalis suspension can be considered as a minimally invasive but very effective and even reversible procedure in “poor responders” to botulinum toxin, with good long-term effect and good acceptance by the patients. Additional treatment with botulinum toxin is required in most patients in order to increase the desirable imbalance between the frontalis and the orbicularis muscle.     

Avian eyelid assay, a new diagnostic method for detecting botulinum neurotoxin serotypes A, B and E.

Based upon botulinum neurotoxins' (BoNT) mechanism of action, a novel, rapid, and sensitive avian eyelid assay was developed to detect Clostridium botulinum neurotoxin serotypes A, B and E in assay buffer and mimic samples. It showed that chick was the most optimal model of 20-selected laboratory, non-laboratory animals. The eyelid closure of chick was the indicator symptom for positive results. The detection limits achieved range from 5 to 250 mouse LD(50) for toxin types A, B, and E in a buffer system and mimic samples. No cross reactivity occurred when using staphylococcal enterotoxin B, diphtheria toxin and nerve agent sarin, but cross reactivity was obtained in more than 6h for using high dose of tetanus toxin. This cross reactivity can be differentiated by BoNT neutralization tests with a serotype-specific antiserum in parallel. The avian eyelid assay can be performed within as short a time as 0.4-6 h. We report here the development of avian eyelid assay is the second animal bioassay for the detection of toxin types A, B, and E which approaches the sensitivity of the mouse bioassay, and is simple to perform as well as rapid to yield results.     

A型肉毒毒素治疗Meige's综合征

目的 评估A型肉毒毒素治疗Meige's综合征的疗效.方法 对A型肉毒毒素治疗的30例Meige's综合征患者资料进行回顾性分析.结果 30例Meige's综合征患者注射A型肉毒毒素后25例完全缓解,5例明显缓解,总有效率100%.起效时间注射当天～第3天.疗效维持平均为5个月.重复治疗有效.局部不良反应轻微、短暂、可逆,无全身不良反应及过敏反应.结论 A型肉毒毒素局部注射是治疗Meige's综合征的一种安全、有效、简便、易行的方法.     

B型肉毒毒素重链C端基因的克隆与表达

目的:扩增B型肉毒毒素重链C端基因并将其在大肠杆菌中表达.方法:首先克隆B型肉毒毒素重链C端片段(BoNTB/Hc),经IPTG诱导,在大肠杆菌中进行天然序列的表达.构建原核表达载体pET32/Hc后进行融合蛋白的表达.对5′端引物进行修饰,最终进行N端修饰蛋白的表达.结果:扩增得到的BoNTB/Hc与已知序列同源性达99%,未得到天然序列的表达,获得了融合蛋白和N端修饰蛋白的表达.Western blot鉴定结果表明,融合蛋白和N端修饰蛋白都可以和特异性抗体发生反应.结论:获得了B型肉毒毒素重链C端基因的表达,为肉毒毒素相关研究奠定了基础.     

A randomized,double-masked,crossover comparison of the efficacy and safety of botulinum toxin type A produced from the original bulk toxin source and current bulk toxin source for the treatment of cervical dystonia

In 1997, the US FDA approved a new bulk toxin source (now referred to as current) for the manufacture of botulinum toxin type A (BTX-A). The current BTX-A preparation has a lower neurotoxin complex protein load than the original BTX-A preparation, which may reduce antigenic potential. The present double-masked, multicenter study compared the efficacy and safety of BTX-A (BOTOX) produced from both original and current bulk toxin sources for the treatment of cervical dystonia. Patients (N = 133) were injected with BTX-A produced from original and current bulk toxin sources using a crossover design. Adverse events were assessed at each visit. Efficacy was assessed at 2 and 6 weeks post-injection using the severity and pain-disability subscales of the Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS). Mean BTX-A doses were comparable (original: 155 U, current: 156 U). Both BTX-A preparations produced similar, statistically significant reductions in TWSTRS severity and pain-disability scores at weeks 2 and 6 post-injection. The original and current BTX-A preparations showed no significant differences in adverse events, including both treatment-related (34%, 31%) and treatment-unrelated (27%, 32%), respectively. BTX-A produced from the original and current bulk toxin sources showed comparable efficacy and safety in the treatment of cervical dystonia; both significantly reduced dystonia severity and pain.     

A型肉毒毒素用于口角歪斜和鼻唇沟不对称的研究

目的 在面瘫患者健侧部分面肌中注射A型肉毒毒素用以矫正口角歪斜和不对称的鼻唇沟，以满足美容的需要。方法 将2001年1月-2005年12月来在门诊和住院的部分面瘫患者作为观察对象，除对照组外治疗组分别在健侧面肌中注射A型肉毒毒素，依据注射剂量随机分为5个治疗组：A组（各肌注射1．25u）、B组（各肌注射2．50u）、C组（各肌注射5．OOu）、D组（降、提口角肌和颧大、小肌各注射2．50U，笑肌注射5．00u）和E组（降、提口角肌和颧大、小肌各注射5．00u，笑肌注射2．50U），3d后定期观测每例患者双侧口角到门齿中缝的距离差。结果 除A组外，各治疗组的口角歪斜和鼻唇沟不对称均得到不同程度的纠正，注射剂量越大起效越快，持续时间越长，但表情动作受到的影响也略大。结论 根据口角歪斜和鼻唇沟不对称的程度，在健侧面肌注射相应剂量的A型肉毒毒素，既可以较好地纠正面瘫患者的口角歪斜和鼻唇沟的不对称，又可以避免并发症的发生。     

Recombinant C fragment of botulinum neurotoxin B serotype (rBoNTB (HC)) immune response and protection in the rhesus monkey

Botulinum neurotoxin B (BoNTB) is a distinct protein subtype of a family of neurotoxins with the potential for use in biological warfare or terrorist attacks. This study is one in a series evaluating the immunogenicity and protective effects of recombinant vaccines against the different subtypes of botulinum toxin. The recombinant subunit vaccines encoding the C fragment portion (50 kDa) of the toxins are produced in the yeast, Pichia pastoris. In this study, groups of rhesus monkeys were vaccinated with three doses (1 and 5 μg per dose) of rBoNTB(H_c) vaccine. Total and neutralizing antibody titers were determined at various times during and postvaccination. Two groups of vaccinated monkeys plus non-vaccinated controls were actively challenged with B toxin by aerosol exposure. All monkeys receiving vaccine were protected from the toxin and no clinical signs of disease were observed, while controls displaying classic signs of botulism succumbed to the toxin challenge. Two additional groups of monkeys receiving the same vaccine regiment as the first two groups had significant levels of circulating neutralizing antibody titers up to 24 months postvaccination. This non-human primate study demonstrated the short- and long-term immunity afforded by the rBoNTB(H_c) vaccine.     

痉挛性发音障碍诊断及治疗的研究

目的对痉挛性发音障碍患者临床特点,喉肌电图表现,疗效进行分析,探讨痉挛性发音障碍诊断及治疗特点。方法对22例痉挛性发音障碍患者治疗前后症状、嗓音声学特征,频闪喉镜下声带状态,喉肌电图特征进行分析;根据不同分型,应用肉毒素A行特定肌肉注射并观察疗效。结果22例痉挛性发音障碍患者中,内收肌型18例(81 8% ),外展肌型4例(18 2% )。内收肌型患者发音嘶哑,音质紧张、言语中断,发音时声带过度内收,杓间区明显,伴局部震颤; 2例患者发音时还同时伴有舌及软腭震颤;肌电图甲杓肌运动单位电位(motorunitpotential,MUP)振幅明显增加(P<0 01),干扰相呈密集束状放电,募集活动异常活跃,幅度明显增大(700~2500μV)。4例外展肌型患者发音低哑、震颤,气息声明显,发音时声门闭合不良;环杓后肌MUP振幅明显增加,在374~538μV间,募集活动异常活跃,幅度增大(3000~5000μV)。内收肌型患者应用肉毒素A进行甲杓肌注射,单侧剂量大于2 5U疗效明显。症状开始改善时间为注射后6h~2d,平均( x±s,下同)为( 1 4±0 8)d, 2周时最为明显,肌电图及喉肌诱发电位显示药物作用完全,注射肌肉失神经支配。疗效维持8~24周,平均维持(15 2±4 9)周,副作用包括不同程度的发音气息声,声门闭合不良,吞咽不适,饮水呛咳。外展肌型患者采用环杓后肌     

应用肉毒毒素A治疗腭肌阵挛性耳鸣临床分析

目的探讨肉毒毒素A对腭肌阵挛源性耳鸣的治疗作用。方法在鼻内窥镜下,将20U肉毒毒素A注射到4例腭肌阵挛性耳鸣患者患侧腭部肌肉内(腭帆张肌、腭帆提肌等),观察患者耳鸣的变化以及是否有并发症出现。同时回顾相关文献,对该病的病因、诊断及治疗加以分析。结果用药后第三天,患者腭部肌肉阵挛和耳鸣均消失,疗效持续约3个月。耳鸣消失的同时出现轻度鼻咽部返流或发声困难,约一周后逐渐消失。结论阵挛的腭部肌肉内注射肉毒毒素A是治疗腭肌阵挛性耳鸣的有效方法。     

肉毒中毒的诊断与治疗

肉毒毒素(BoNT)是最强的神经毒素,能够通过抑制神经肌肉接头处乙酰胆碱的释放而引起肌肉麻痹,产生相应的临床症状.其中食物性肉毒中毒最常见,重度中毒者可因呼吸衰竭而死亡.为提高临床医生对肉毒毒素中毒的认识,尽早诊治该病,本文重点对肉毒中毒的临床表现及治疗方法进行介绍.